Using the pyrrolizidine alkaloid, indicine N-oxide, a clinically used antitumor agent, as a model we have prepared the semisynthetic analog which as a disastereomeric mixture was 10 x as active as indicine N-oxide. Using the necine bases retronecine and heliotridine readily obtained from natural sources, we plan to regioselectively prepare C-9 esters from optically pure chiral acids. In addition, we plan to utilize asymmetric syntheses to reduce Alpha-ketoesters to prepare tghe desired Alpha-hydroxyesters. Our aims are to provide improved antitumor agents modeled after indicine N-oxide by utilizing a structure-activity approach to understand the mechanism of action.